This invention relates to reagents and methods for targeting at least one diagnostic or therapeutic agent to an inflammatory or infectious lesion. Polyspecific antibody composites specific for at least two different leukocyte cell types are conjugated to at least one diagnostic or therapeutic agent for use in the present invention.
It has been recognized that, since leukocytes accumulate in large numbers at localized sites of infection or inflammation, it might be feasible to detect such sites by removing leukocytes from the blood, labeling them with an appropriate indicator, conventionally In-111, and returning them to the blood. After a period of time has passed sufficient to allow the labeled leukocytes to redistribute in the body, the subject is scanned with suitable equipment to detect localization of the labeled leukocytes. While effective, the method described above is substantially time consuming since time is required for the leukocyte separation, labeling and, particularly redistribution in the body after re-injection.
In U.S. Pat. No. 4,634,586 (Goodwin et al.), incorporated herein by reference in its entirety, leukocytes are radioimmunoimaged by injecting patients with an immunoreactive nonleukocidal conjugate of an anti-leukocyte monospecific antibody and a gamma emitting radioactive metal chelate, waiting for the conjugate to localize on the leukocytes, injecting a patient with an antibody to the conjugate to clear the blood of background nonlocalized conjugate, and visualizing the leukocytes by scintillation scanning.
Leukocyte imaging has been severely limited in the prior art due to poor target to background ratio. It has been shown that the localization ratio can be increased by using second antibody clearance. However, the target to background ratio remains a problem, because each targeting antibody only binds to a specific leukocyte cell type, either a granulocyte, a monocyte, a B-lymphocyte or a T-lymphocyte. Therefore, there will be many antibodies that are highly reactive and specific for a particular leukocyte cell in the background that have not bound to the target site, because that particular leukocyte cell type is not present in appreciable concentration at the site of infection or inflammation.
A need therefore continues to exist for a method of targeting an imaging or therapy agent to an inflammatory or infectious lesion with higher efficiency and enhanced target to background ratio to permit more effective detection and/or treatment of the lesion.